A Phase III Trial of Hypofractionated External Beam Image-Guided Highly Targeted Radiotherapy: The HEIGHT Trial

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2015 by University of Miami
Sponsor:
Information provided by (Responsible Party):
Alan Pollack, University of Miami
ClinicalTrials.gov Identifier:
NCT01411332
First received: August 3, 2011
Last updated: August 5, 2015
Last verified: August 2015

August 3, 2011
August 5, 2015
May 2011
May 2017   (final data collection date for primary outcome measure)
To compare the rate of prostate biopsy positivity after HTIMRT to SIMRT at 2 years after all therapy. [ Time Frame: 2 - 2.5 years post-therapy ] [ Designated as safety issue: No ]
The proportion of positive biopsy findings among patients without clinical or biochemical failure 2-2.5 years after completing study treatment (RT or ADT, whichever is longer).
Same as current
Complete list of historical versions of study NCT01411332 on ClinicalTrials.gov Archive Site
  • Number of patients with, and severity of, acute and late adverse events in an HT boost clinical trial. [ Time Frame: 5.25 years ] [ Designated as safety issue: Yes ]
    Number of patients with, and severity of, acute and late adverse events in an HT boost clinical trial.
  • To evaluate the influence of HTIMRT to health-related quality of life (HRQOL), prostate cancer-specific anxiety and prostate cancer-specific QOL. [ Time Frame: 5.25 years ] [ Designated as safety issue: No ]
    Two contemporary instruments (questionnaires) will be utilized to assess patient function and bother (Expanded Prostate Cancer Index Composite-SF12 (EPIC-SF12) and the prostate cancer-specific anxiety Memorial Anxiety Scale for Prostate Cancer patients (MAX-PC).
  • To quantify biomarker expression in different prostate tumor regions, comparing specifically the DCE-MRI enhancing and non-enhancing regions. [ Time Frame: 5.25 years ] [ Designated as safety issue: No ]
    Quantification of the amount of the biomarker specific immunohistochemical staining in the area of tumor.
  • To evaluate the incidence and relationship of circulating free DNA and tumor cells to tissue biomarkers and prostate biopsy positivity at 2 years after completion of therapy. [ Time Frame: 2 years post-completion of therapy ] [ Designated as safety issue: No ]
    The investigators test whether absolute pretreatment CTC counts and treatment-induced changes in CTC counts as assessed on our novel microfilter platform correlate with response to therapy (biopsy positivity at two years after treatment).
  • Biochemical failure or clinical failure [ Time Frame: 5.25 years ] [ Designated as safety issue: No ]
    The cumulative incidence of biochemical or clinical failure allowing for competing risk as needed. Clinical failure is defined as at least a 25% increase in the size of the tumor relative to the smallest volume recorded, or new extension of tumor beyond the capsule, or re-extension of tumor beyond the capsule after initial regression, or urinary obstructive symptoms with carcinoma found at TURP. Biochemical failure is defined as PSA ≥ nadir + 2 ng/mL.
  • Failure-free Survival (FFS) [ Time Frame: 5.25 years ] [ Designated as safety issue: No ]
    The elapsed time from start of radiotherapy to first documented evidence of biochemical or clinical failure or death from any cause, whichever occurs first. In the absence of any event defining failure, follow-up time will be censored at the date of last documented failure-free status.
  • Overall Survival (OS) [ Time Frame: 5.25 years ] [ Designated as safety issue: No ]
    The elapsed time from start of radiotherapy to death from any cause. For surviving patients, follow-up will be censored at the date of last contact.
Same as current
Not Provided
Not Provided
 
A Phase III Trial of Hypofractionated External Beam Image-Guided Highly Targeted Radiotherapy: The HEIGHT Trial
A Phase III Trial of Hypofractionated External Beam Image-Guided Highly Targeted Radiotherapy: The HEIGHT Trial
  1. Delivery of directed hypofractionated targeted (HT) radiotherapy (RT) tumor boost to the dominant tumor lesion in the prostate as identified by multiparametric MRI will increase tumor eradication from the prostate.
  2. Biomarker expression levels differ in the multiparametric MRI defined regions at high risk of harboring tumors that determine outcome.
  3. 10-15% of men undergoing RT have Circulating DNA or tumor cells (CTC) that are related to an adverse treatment outcome.
  4. Quality of life will not differ significantly between the treatment arms.
  5. Prostate cancer-related anxiety will be reduced in the HTIMRT arm, because the patients will be aware that the dominant tumor will be targeted with higher radiation dose.
Not Provided
Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Prostate Cancer
  • Prostate Adenocarcinoma
  • Radiation: Standard Fractionated Intensity Modulated Radiotherapy (SIMRT)
    A total dose of 80 Gy will be delivered in 40 fractions to the Clinical Target Volume (CTV).
  • Radiation: Hypofractionated Targeted Intensity Modulated Radiotherapy (HTIMRT)
    Dose escalation to the Dynamic Contrast Enhanced MRI (DCE-MRI)-defined dominant region(s) by dose painting at 2.35 Gy per fraction, while the rest of the Clinical Target Volume (CTV) receives 2.0 Gy a fraction to 76 Gy. The hypofractionated targeted (HT) boost region will receive an absolute dose of 89.3 Gy. Assuming an α/β ratio of 3.0, this would be equivalent to 95.5 Gy in 2.0 Gy fractions.
  • Behavioral: EPIC SF-12 Questionnaire
    Expanded Prostate Cancer Index Composite-SF12 (EPICSF-SF12) quality of life questionnaire prior to radiation therapy, during the last week of radiation therapy, 6 weeks, 3 months, 9 months, 15 months, and yearly up to 5.25 years after radiation therapy.
  • Behavioral: MAX-PC Questionnaire
    Expanded Prostate Cancer Index Composite-SF12 (EPICSF-SF12) quality of life questionnaire prior to radiation therapy, during the last week of radiation therapy, 6 weeks, 3 months, 9 months, 15 months, and yearly up to 5.25 years after radiation therapy.
  • Behavioral: IPSS Questionnaire
    International Prostate Symptom Score (IPSS) questionnaire prior to radiation therapy, during last week of radiation therapy, 6 weeks, 3 months and every 6 months up to 5.25 years post-radiation therapy.
  • Procedure: Ultra-Sound Guided Biopsy
    Ultra-Sound Guided Biopsy prior to radiation therapy and 2 - 2.5 years post-completion of radiation therapy.
  • Procedure: Prostate Fiducial Marker Placement
    Prostate Fiducial Marker implanted in prostate tissue during Ultrasound Guided Biopsy prior to radiation therapy, within 4 weeks after enrollment.
  • Procedure: Blood Sample Collection
    Plasma and serum sample collection prior to radiation therapy, during last week of radiation therapy, 3 months post-radiation therapy and within 2 months of 2 year Ultrasound-Guided prostate biopsy.
  • Procedure: DCE-MRI
    Dynamic Contrast Enhanced MRI of Pelvis/Prostate prior to radiation therapy. 3 months post-completion of radiation therapy, and within 2 months of 2 year Ultrasound guided prostate biopsy
  • Procedure: CT Simulation
    CT Simulation prior to radiation therapy.
  • Procedure: MRI Simulation
    MRI Simulation prior to radiation therapy.
  • Procedure: Bone Scan
    Bone Scan as needed
  • Active Comparator: Arm I: SIMRT
    Arm I: Standard Fractionated Intensity Modulated Radiotherapy (SIMRT)
    Interventions:
    • Radiation: Standard Fractionated Intensity Modulated Radiotherapy (SIMRT)
    • Behavioral: EPIC SF-12 Questionnaire
    • Behavioral: MAX-PC Questionnaire
    • Behavioral: IPSS Questionnaire
    • Procedure: Ultra-Sound Guided Biopsy
    • Procedure: Prostate Fiducial Marker Placement
    • Procedure: Blood Sample Collection
    • Procedure: DCE-MRI
    • Procedure: CT Simulation
    • Procedure: MRI Simulation
    • Procedure: Bone Scan
  • Active Comparator: Arm II: HTIMRT
    Arm II: Hypofractionated Targeted Intensity Modulated Radiotherapy (HTIMRT)
    Interventions:
    • Radiation: Hypofractionated Targeted Intensity Modulated Radiotherapy (HTIMRT)
    • Behavioral: EPIC SF-12 Questionnaire
    • Behavioral: MAX-PC Questionnaire
    • Behavioral: IPSS Questionnaire
    • Procedure: Ultra-Sound Guided Biopsy
    • Procedure: Prostate Fiducial Marker Placement
    • Procedure: Blood Sample Collection
    • Procedure: DCE-MRI
    • Procedure: CT Simulation
    • Procedure: MRI Simulation
    • Procedure: Bone Scan
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
72
May 2017
May 2017   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Biopsy confirmed adenocarcinoma of the prostate.
  • T1-T3a disease based on digital rectal exam.

    1. T1a is permitted if peripheral zone biopsies are positive.
    2. T3a disease based on MRI is acceptable.
  • No evidence of metastasis by any clinical criteria or available radiographic tests.
  • Gleason score 6-8.
  • Patients with Gleason score 8 must be offered long term androgen deprivation therapy (ADT) and refuse such treatment because only 4-6 (±2 months) months (short term ADT) is permitted on this protocol. Gleason score ≥ 8 patients should be recommended to receive short term ADT in conjunction with RT. When given, the ADT recommended to begin after fiducial marker placement, if applicable; however, ADT is permitted to have been started up to two months prior to the signing of consent.

    1. Patients with Gleason score 8 disease must have <40 of the diagnostic tumor tissue involved with tumor.
    2. Patients with Gleason score ≤7 may be treated with 4-6 (±2 months) months of ADT.
  • PSA ≤30 ng/mL within 3 months of enrollment. If PSA was above 30 and dropped to <30 with antibiotics, this is acceptable for enrollment.
  • If PSA is >15 ng/ml or there is ≥ Gleason 8 disease, a bone scan should be obtained ≤4 months before enrollment and should be without evidence of metastasis. A questionable bone scan is acceptable if plain x-rays, CT and/or MRI are negative for metastasis.
  • No previous pelvic radiotherapy
  • No previous history of radical/total prostatectomy (suprapubic prostatectomy is acceptable)
  • No concurrent, active malignancy, other than nonmetastatic skin cancer or early stage chronic lymphocytic leukemia (well-differentiated small cell lymphocytic lymphoma). If a prior malignancy is in remission for ≥ 5 years then the patient is eligible.
  • Identifiable multiparameter functional MRI defined tumor lesion or lesions using a 1.5T or 3.0T MRI (3.0T preferable), that total in volume <33% of the prostate within 3 months prior to enrollment.

    a. Multiparametric functional including DWI of prostate and pelvis is required prior to protocol consideration

  • Ability to understand and the willingness to sign a written informed consent document
  • Zubrod performance status <2 (Karnofsky or ECOG performance status may be used to estimate Zubrod)
  • Willingness to fill out quality of life/psychosocial forms.
  • Age ≥35 and ≤85 years.
  • Serum testosterone is within 40% of normal assay limits (e.g., x=0.4*lower assay limit and x=.04*upper assay limit + upper assay limit),, taken within 4 months of enrollment. Patients who have been started on ADT prior to signing consent are not required to have a serum testosterone at this level prior to signing consent; but, a serum testosterone prior to fiducial marker placement is recommended.
  • Serum LFTs taken within 3 months of enrollment.
  • Complete blood counts taken within 3 months of enrollment.

Exclusion Criteria

  • Previous pelvic radiotherapy.
  • Previous history of radical prostatectomy.
  • Concurrent, active malignancy, which is not nonmetastatic skin cancer or early stage chronic lymphocytic leukemia (well-differentiated small cell lymphocytic lymphoma). If a prior malignancy is in remission for < 5 years then the patient is not eligible
  • Not willing to fill out quality of life/psychosocial questionnaires.
Male
35 Years to 85 Years
No
United States
 
NCT01411332
20100635
Yes
Alan Pollack, University of Miami
University of Miami
Not Provided
Principal Investigator: Alan Pollack, MD, PhD University of Miami
University of Miami
August 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP